| 1. |
- Biermann, Jana, et al.
(författare)
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A 17-marker panel for global genomic instability in breast cancer.
- 2020
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 112:2, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- Genomic instability is a hallmark of cancer that plays a pivotal role in breast cancer development and evolution. A number of existing prognostic gene expression signatures for breast cancer are based on proliferation-related genes. Here, we identified a 17-marker panel associated with genome stability. A total of 136 primary breast carcinomas were stratified by genome stability. Matched gene expression profiles showed an innate segregation based on genome stability. We identified a 17-marker panel stratifying the training and validation cohorts into high- and low-risk patients. The 17 genes associated with genomic instability strongly impacted clinical outcome in breast cancer. Pathway analyses determined chromosome organisation, cell cycle regulation, and RNA processing as the underlying biological processes, thereby offering options for drug development and treatment tailoring. Our work supports the applicability of the 17-marker panel to improve clinical outcome prediction for breast cancer patients based on a signature accounting for genomic instability.
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| 2. |
- Bülow, Erik, et al.
(författare)
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Are the First or the Second Hips of Staged Bilateral THAs More Similar to Unilateral Procedures? A Study from the Swedish Hip Arthroplasty Register
- 2020
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Ingår i: Clinical Orthopaedics and Related Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-921X .- 1528-1132. ; 478:6, s. 1262-1270
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Tidskriftsartikel (refereegranskat)abstract
- Background Bilateral THAs performed in the same patient should not be considered independent observations, neither biologically nor statistically. As a result, when surgical results are reviewed, it is common to analyze only the first of the two hips, assuming that the first, and not the second hip of a staged bilateral THA, better resembles unilateral THAs. This assumption has not been empirically justified. Question/purposes (1) In patients with staged bilateral THA, is the first or second hip more similar to a unilateral THA in terms of age at surgery, presence of any preoperative Charlson comorbidity, and risk of postoperative reoperation? (2) Should the date of a first or second hip surgery of a staged bilateral THA be used as a starting point for patient survival to better resemble patients with unilateral THA? Methods We identified 68,357 THAs due to osteoarthritis in 63,613 patients from the Swedish Hip Arthroplasty Register (SHAR) in 1999-2015. Of those THAs, 14,780 concerned the first hip of a staged bilateral procedure performed between 1999 and 2004; 28,542 were unilaterals from 2004 to 2008, and 25,035 concerned the second hip of a staged bilateral procedure performed 2008 to 2015. We excluded patients who underwent one-stage bilateral THAs. We used different inclusion periods to distinguish unilateral procedures from the first and second hips from staged bilateral procedures because sufficiently long set-up and follow-up periods were needed before and after each period to identify possible contralateral THAs. This introduced potential period confounding, meaning that possible group differences might not be distinguished from unrelated outcome differences over time. We investigated if such time trends existed. It did not for age and reoperation rates, but it did for comorbidity and patient survival. Our primary study endpoint was whether patients with unilateral THAs were more similar to patients with a first hip of a staged bilateral THA, or to patients with their second hip operated. We used Student's t-test to compare mean age at surgery. The proportion of patients with at least one presurgery Charlson comorbidity were compared by 95% bootstrap confidence intervals, after subtracting the yearly time-trend to avoid period confounding. Postoperative risks of reoperation were compared by log-rank tests of Kaplan-Meier curves and by comparing 5-year reoperation rates by pair-wise 95% CIs. Our secondary study endpoint was to compare patient survival for patients with a unilateral THA, a first hip of a staged bilateral THA, or a second hip of a staged bilateral THA. We evaluated this by relative 5-year survival, comparing patients of each group with the general Swedish population of the same age, sex, and year of birth. This way, possible survival differences would be less likely explained by period confounding. Results Patients undergoing unilateral THA were older than those undergoing a first hip of a staged bilateral THA (70 +/- 10 versus 66 +/- 9 years, mean difference of 4; p < .001), but they were not different from patients undergoing the second hip of a staged bilateral THA (70 +/- 9 years, mean difference of 0; p = 0.74). The period-adjusted proportion of patients with unilateral THA and presurgery comorbidity (Charlson index > 0) was 20% (95% CI: 19.8-20.7). This was no different from patients with a second hip from a staged bilateral THA (20%; 19.7-20.6), but higher compared to patients with a first hip of a staged bilateral THA (15%; 14.5-15.4). For reoperation rates, the log-rank tests showed no difference between unilateral THAs and the second hips of staged bilateral THAs (). Such difference was found for unilaterals compared with the first hips of staged bilateral THAs (). The Kaplan-Meier estimate of reoperation rates at 5 years after surgery were also no different for the unilateral THAs compared with the second hips of staged bilateral THAs (3% [95% CI 2.8 to 3.2] for both groups). It was lower (2% [95% CI 1.8 to 2.3]) for a first hip of a staged bilateral THA. For the secondary outcome, the relative 5-year survival differed for all groups. It was 105% (95% CI 104.9 to 105.9) for patients with unilateral THA, 107% (95% CI 106.3 to 107.4) for patients with a second hip from a staged bilateral THA and 109% (95% CI 108.8 to 109.5) for patients with a first hip of a staged bilateral THA. Patients with only a first hip of a planned staged bilateral THA who did not survive long enough to undergo their second THA were classified as unilaterals. The rank-order of survival curves are therefore by design ("immortal time bias"). We conclude, however, that survival for patients with unilateral THA more closely resembles the survival of patients with a second hip of a staged bilateral THA, compared with the first. Conclusions Our findings, which are based on observational register data, challenge the common practice in epidemiologic studies of analyzing only the first hip of a staged bilateral THA. We recommend analyzing the second THA in a patient who has undergone staged bilateral THA rather than the first because the second procedure better resembles unilateral THA.
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| 3. |
- Eneqvist, T., et al.
(författare)
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Does the order of total hip replacement and lumbar spinal stenosis surgery influence patient-reported outcomes: An observational register study
- 2021
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 39:5, s. 998-1006
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Tidskriftsartikel (refereegranskat)abstract
- Patients with degenerative hip and lumbar spine disorders requiring surgery in both locations is fairly common in clinical practice. We investigated if the order of total hip replacement (THR) and lumbar spinal stenosis surgery (LSSS) influences patient-reported outcomes (PROs). We used data from the Swedish Hip Arthroplasty Register (SHAR) and the Swedish Spine Register (Swespine), on patients operated with THR and LSSS in years 2002 to 2012. To increase the probability of having symptomatic disorders in both locations at the time of the first surgery, we only included patients with both LSSS and THR performed within 2 years. Linear and logistic regression analyses adjusted for age, sex, preoperative PROs, and time between surgeries were used to investigate the association between order of surgeries and the generic PRO measurements EQ-5D and EQ VAS. Eighty-four patients had THR prior to LSSS and 171 patients LSSS prior to THR. Linear regression showed that LSSS prior to THR was associated with higher EQ-5D index (B = 0.09, 95% confidence interval [CI] 0.03-0.16) and EQ VAS (B = 5.6, 95% CI 0.4-10.9) 1 year after the last surgery. Logistic regression showed that the odds ratio [OR] for not having any problems in the "pain" (OR = 3.0, 95% CI 1.5-6.3) and "anxiety/depression" (OR = 2.3, 95% CI 1.3-4.1) dimensions were higher for LSSS before THR. In our cohort, LSSS before THR was associated with better health-related quality of life outcomes compared to the reverse order. The results from our cohort can be helpful in a clinical situation where the physician gives advice to an individual patient when choosing the order of procedures. However, further studies are necessary in order to confirm these results in other cohorts. At present, standard of care remains that order of surgery should be individualized for each patient, with guidance from the operating surgeons.
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| 4. |
- Eneqvist, Ted, 1982, et al.
(författare)
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How do EQ-5D-3L and EQ-5D-5L compare in a Swedish total hip replacement population?
- 2020
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:3, s. 272-278
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - To better detect small changes in postoperative outcome following total hip replacement (THR), the Swedish Hip Arthroplasty Register (SHAR) has decided to change from the EQ-5D-3L (3L) to the EQ-5D-5L (5L). To enable comparison of results obtained with use of the 2 versions of EQ-5D, transferal of results between the questionnaires used is necessary. We assessed the measurement properties of the EQ-5D-5L compared with the EQ-5D-3L, preoperatively and 1-year postoperatively in a Swedish THR population. Patients and methods - Patients eligible for elective THR during 2015 in Western Sweden were invited to the study. With a 2-week separation, the 3L and 5L questionnaires were administered to patients before and 1 year after surgery. Comparing the 2 versions of the EQ-5D, we investigated redistribution of responses, ceiling and floor effects, EQ VAS correlations (Spearman's rank correlation coefficient, r(s)), and EQ VAS scores for different severity levels by dimension (univariable ordinary least square regression). Results - The additional severity levels of the 5L version were frequently used on both measurement occasions (preoperative mobility 5%, self-care 17%, usual activities 20%, pain 5% and anxiety 3%, postoperative mobility 6%, self-care 5%, usual activities 8%, pain 9%, and anxiety 5%). Ceiling effects of the 3L version diminished overall by 7% using the 5L version. The correlations between the 2 EQ VAS scores obtained with the 3L and 5L instruments were strong both pre- (r(s) = 0.71) and postoperatively (r(s) = 0.87). Estimated EQ VAS scores for different levels of severity were consistent for all dimensions except for the mobility dimension of the preoperative 5L version and the anxiety dimension in the postoperative 5L version. Interpretation - Our findings support that the 5L has a higher resolution than the 3L version regarding description of health-related quality of life in patients undergoing THR in Sweden. The EQ VAS scores for different levels of severity agree well between the EQ-5D versions. This could potentially be used to develop a crosswalk value set for transforming 3L to 5L responses in this patient group.
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| 5. |
- Nemes, Szilard, 1977, et al.
(författare)
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A Brief Overview of Restricted Mean Survival Time Estimators and Associated Variances
- 2020
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Ingår i: Stats. - : MDPI AG. - 2571-905X. ; 3:2, s. 107-119
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Tidskriftsartikel (refereegranskat)abstract
- Restricted Mean Survival Time ( R M S T ) experiences a renaissance and is advocated as a model-free, easy to interpret alternative to proportional hazards regression and hazard rates with implication in causal inference. Estimation of R M S T and associated variance is mainly done by numerical integration of Kaplan–Meier curves. In this paper we briefly review the two main alternatives to the Kaplan–Meier method; analysis based on pseudo-observations, and the flexible parametric survival method. Using computer simulations, we assess the efficacy of the three methods compared to a fully parametric approach where the distribution of survival times is known. Thereafter, the three methods are directly compared without any distributional assumption for the survival data. Generally, flexible parametric survival methods outperform both competitors, however the differences are small.
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| 6. |
- Ray, G. S., et al.
(författare)
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Changes in health-related quality of life are associated with patient satisfaction following total hip replacement: an analysis of 69,083 patients in the Swedish Hip Arthroplasty Register
- 2020
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 91:1, s. 48-52
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Total hip replacement (THR) aims mainly to improve quality of life via restoration of hip function and provision of pain relief. This study sought to assess whether improvements in quality of life between the preoperative and 1-year postoperative period were associated with patient satisfaction Patients and methods - Data were extracted for 69,083 THR operations with complete data reported to the Swedish Hip Arthroplasty Register (SHAR) between 2008 and 2015. Health-related quality of life and patient satisfaction were captured using the Euro-Qol-5D (EQ-5D) and visual analogue scale (VAS), respectively. Multivariable analysis was performed to assess associations between the changes in pre- and postoperative EQ5D and patient satisfaction. Results - In patients reporting severe or moderate problems with mobility preoperatively, improvement to no problems was associated with numerically higher patient satisfaction (coefficient -18 [95% CI -22 to -14] and -18 [-18 to -17]). Improvement in the self-care dimension from severe or moderate problems to no problems was associated with numerically higher patient satisfaction (-15 [-16 to -14] and -13 [-15 to -11]). Improvement from severe problems with the ability to perform usual activities to no problems was associated with numerically higher patient satisfaction (-18 [-19 to -17]). This association was also found for improvement in pain/discomfort and anxiety/depression (-16 [-17 to -15] and -15 [-16 to -14]). Interpretation - Our results indicate that satisfaction with the operated hip is a valid patient-reported outcome reflecting the changes in different EQ-5D dimensions and should be included in the follow-up of patients after THR surgery.
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| 7. |
- Tzikas, Anna-Karin, 1977, et al.
(författare)
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A comparison between young and old patients with triple-negative breast cancer: biology, survival and metastatic patterns
- 2020
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 182, s. 643-654
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To determine the biology, recurrence rate, metastatic patterns and survival times in primary triple-negative breast cancer (TNBC) with focus on the comparison between younger and elderly patients. Methods Patients with primary TNBC stage I-IV diagnosed from 2007 to 2015 were identified and information on tumor biology, stage, treatment, recurrences and death recorded. Results A total of 524 patients, median age 60 years (range 24-94) with a median follow-up of 55 months (range 0-129) were identified. Stage was similar in younger (< 40 years) (n = 58) and older (> 74 years) (n = 96) patients (p = 0.37). A statistically significant difference was found concerning histopathologic grade (p = 0.006) and Ki67 (median 80% versus 70%;p = 0.002) but not for LVI (p = 0.9) with more aggressive tumors among younger patients. Adjuvant/neoadjuvant chemotherapy was more frequently given to younger compared with older patients (96% versus 12%;p = 0.0005). Only brain (p = 0.016) and liver (p = 0.047) metastases were more often registered among younger patients while other locations were similar. Shorter survival times, recurrence-free survival (RFS), distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) were found in the older group, although not after adjusting for adjuvant/neoadjuvant chemotherapy. Most deaths (68%) in the older group were caused by TNBC. When comparing patients > 75 years (n = 92) with <= 75 years (n = 432), a worse outcome among older was also observed: RFS (p = 0.00012), DDFS (p = 0.00041), BCSS (p < 0.0001) and survival following distant metastasis (p = 0.0064) Conclusions Primary TNBC in younger patients is more often of poor differentiation grade and highly proliferative compared with older patients. The majority of older patients still have grade III tumors with a Ki67 > 60% and outcome is poor. Few older patients in our study were treated with chemotherapy both in adjuvant and palliative setting, underlining the need for more prospective trials and treatment options suitable for this patient population.
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| 8. |
- Werner Rönnerman, Elisabeth, 1970, et al.
(författare)
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Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma.
- 2022
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer (OC) is the leading cause of gynecological cancer-related death. Of the main OC histologic subtypes, invasive mucinous carcinomas (MC) account for only 3% of OC cases and are frequently associated with favorable prognosis. Nevertheless, MCs differ greatly from the other OC histotypes in clinical, pathological, and biological behavior. However, the origin and molecular pathogenesis of MC are not yet fully understood. Therefore, identification of novel diagnostic markers could potentially facilitate early diagnosis of OC, particularly the MC histotype, thereby leading to the development of histotype-specific treatment regimens and improved survival rates.In the present study, Trefoil factor gene family members (TFF1, TFF2 and TFF3) were identified as MC histotype-specific biomarkers using RNA sequencing (RNA-seq) data for 95 stage I-II OCs. The diagnostic value of TFF1, TFF2 and TFF3 was then evaluated by immunohistochemistry on 206 stage I-II OCs stratified by histotype (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], clear cell carcinoma [CCC], and MC).We showed significantly elevated intracytoplasmic protein expression levels for TFF1, TFF2 and TFF3 in MC samples, thereby revealing an association between expression of Trefoil factor gene family members and the MC histotype. Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype.Taken together, these findings suggest that the TFF proteins may play a pivotal role in tumor initiation and progression for the MC histotype. Moreover, these novel histotype-specific diagnostic biomarkers may not only improve patient stratification of early-stage ovarian carcinomas but may also be candidates for the development of molecular targeted therapies.
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